The studies presented in this report were designed to further investigate the causal association between phytoestrogen action and increase in sex hormone-binding globulin (SHBG) levels. Phytoestrogens include isoflavones that bind to estrogen receptors and therefore exert estrogenic action. This study included 20 postmenopausal women that ingested 30 g soy milk daily for 10 weeks. Plasma concentrations of isoflavones and SHBG were measured. Total isoflavones significantly increased from 0.014 +/- 0.01 micromol/L (baseline) to 0.53 +/- 0.19 ,micromol/L, and paired responses showed that some subjects clearly increased their SHBG levels. The percent change in SHBG showed a positive correlation with phytoestrogen concentration; all women who had circulating phytoestrogen levels above 0.6 micromol/L increased by at least 30% their SHBG values. Results suggest that phytoestrogens may significantly increase SHBG in subjects whose SHBG concentrations are in the low end of the concentration range.